Alzheimer's disease is currently diagnosed by carrying out an interview with a specialized physician and evaluating the degree of brain atrophy using MRI or the like. However, it is difficult to obtain an objective and correct diagnostic conclusion by interview only. Furthermore, it is impossible to identify a so-called pre-patient, before the onset of symptoms. Additionally, apparatuses such as MRI apparatuses are expensive and consequently can be used only in large special hospitals.
Under such circumstances, biochemical diagnosis using a marker is adopted as a simple and objective method. Among main markers for Alzheimer's disease, intracellular tau protein and β-amyloid (hereinafter referred to as “Aβ”) are known at present (Non-Patent Document 1 and Non-Patent Document 2).
Tau protein is a component constituting microtubules in nerve cells and is leaked out from the cells when the nerve cells are degenerated during an Alzheimer's disease process. As a result, tau protein is detected in cerebrospinal fluid, and is a useful marker. However, tau protein cannot be detected until the condition of the disease progresses. Furthermore, since the leakage amount is small, tau protein is hardly detected in body fluid (for example, blood) other than the cerebrospinal fluid.
Aβ is a causative substance of Alzheimer's disease. Therefore, Aβ can be a most effective marker provided that a quantitative change (an increase in the production) or a qualitative change (an increase in the ratio of highly aggregative Aβ can be precisely measured. However, since Aβ shows aggregative nature, the amount of Aβ detected in a patient's cerebrospinal fluid is rather lower than that of healthy subjects.
Non-Patent Document 1: “Decreased beta-amyloid 1-42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease”; Sunderland, T., Linker, G., Mirza, N., Putnam, K. T., Friedman, D. L., Kimmel, L. H., Bergeson, J., Manetti, G. J., Zimmermann, M., Tang, B., Bartko, J. J., and Cohen, R. M. JAMA 2003, 289, 2094-2103.
Non-Patent Document 2: “Cerebrospinal fluid biomarkers for disease stage and intensity in cognitively impaired patients”; Wahlund, L. O., and Blennow, K. Neurosci. Lett. 2003, 339, 99-102.